Modern tattoo inks generally include organic pigment particles ranging in size from about 200 nanometers to about 5 micrometers. They are typically inserted into the papillary and superficial dermis by a rapidly reciprocating needle. Following injection, the tattoo ink pigment particles reside in the interstitial space between dermal cells for about 24–72 hours, although in some cases pigment particles may reside in interstitial spaces for up to two weeks. Eventually, dermal cells (typically fibroblasts or macrophages) engulf the pigment particles. Once the pigment particles have been engulfed, they usually reside within the cell cytoplasm. The dermal cells typically have low motility, which accounts for the relative permanence of most tattoo images.
Recently, tattoos have become increasingly popular. For instance, the tattoo industry ranked sixth in a 1996 study that estimated the growth rates of various industries (Brown et al., J. School Health 70(9):355 (2000)). The practice of permanent tattooing has become so widespread that it is now estimated that as many as 30 million people in the Western world have at least one tattoo (Baumier et al., Lasers in Surgery and Medicine 26:13–21 (2000)).
Some who choose to be tattooed may at some later date regret the decision. The spirit, motivation, and/or circumstances that compelled one to obtain a tattoo can fade. In some cases, a tattoo that was appropriate or desirable at one station of life may be less appropriate or less desirable at a later date. Depending upon the nature and extent of the tattoo image, an unwanted tattoo may be a nuisance, a source of embarrassment, or even a source of social stigmatization. Perhaps as a direct result of the increased popularity of tattoos, interest in tattoo removal also is increasing. Market estimates suggest that in the year 2000 as many as 410,000 people underwent a tattoo removal procedure. As the recently tattooed population ages, it is expected that the number of those seeking removal of a tattoo will increase.
Current treatment options for tattoo removal include a variety of lasers, dermabrasion, salabrasion, surgical excision, and cryotherapy. Although some treatments may be effective, they may be expensive, time consuming, and painful. In some cases, such treatments also may result in cosmetically undesirable scarring.
One of the more effective tattoo removal treatments is a laser surgical technique in which the tattooed region is irradiated with a high-energy, pulsating laser beam. The tattoo ink pigments absorb a portion of the laser radiation. As a consequence, the pigment particles become sufficiently hot that they decompose into smaller fragments (Ferguson, J. E. et al., British Journal of Dermatology 137: 405–410 (1997)). In the process, the cellular integrity of the surrounding dermal cells may be destroyed. A single laser treatment results in some fading of the tattoo because the human immune system is able to remove some of the pigment fragments (Wheeland, Lasers in Surgery and Medicine 16:2–23 (1995); Zelickson et al., Lasers in Surgery and Medicine 15:364–372 (1994)); however, most pigment fragments become re-engulfed by still intact dermal cells and so remain visible (Ferguson et al., British Journal of Dermatology 137:405–410 (1997)). In nearly all cases, patients are not satisfied with the results of the first laser treatment and they usually return for additional treatments.
Irradiating the tattooed region with enough energy to fragment the tattoo ink pigments can cause a painful burn to form on the skin. Consequently, laser treatments are sometimes spaced at least one month apart in order to afford the skin time to heal. Often, as many as nine such treatments may be required to sufficiently fade the tattoo, resulting in substantial pain and financial cost.
The laser treatment procedure may be ineffective for removing certain colors and may, instead of removing an image, transform some colors such as, for example, transforming a red lipstick tattoo to a black shade that can be very difficult to remove by laser surgical treatment (Jimenez et al., Dermatolog. Surg. 28:177–179 (2002)).
Immune response modifiers (“IRMs”) are compounds that possess potent immunomodulating activity such as, for example, antiviral and/or antitumor activity. Certain IRMs modulate the production and secretion of cytokines. For example, certain IRM compounds induce the production and secretion of cytokines such as, e.g., Type I interferons, TNF-α, IL-1, IL-6, IL-8, IL-10, IL-12, MIP-1, and/or MCP-1. As another example, certain IRM compounds can inhibit production and secretion of certain TH2 cytokines, such as IL-4 and IL-5. Additionally, some IRM compounds are said to suppress IL-1 and TNF (U.S. Pat. No. 6,518,265).
Certain IRMs are small organic molecules (e.g., molecular weight under about 1000 Daltons, preferably under about 500 Daltons, as opposed to large biological molecules such as proteins, peptides, and the like) such as those disclosed in, for example, U.S. Pat. Nos. 4,689,338; 4,929,624; 4,988,815; 5,037,986; 5,175,296; 5,238,944; 5,266,575; 5,268,376; 5,346,905; 5,352,784; 5,367,076; 5,389,640; 5,395,937; 5,446,153; 5,482,936; 5,693,811; 5,741,908; 5,756,747; 5,939,090; 6,039,969; 6,083,505; 6,110,929; 6,194,425; 6,245,776; 6,331,539; 6,376,669; 6,451,810; 6,525,064; 6,541,485; 6,545,016; 6,545,017; 6,558,951; 6,573,273; 6,656,938;.6,660,735; 6,660,747; 6,664,260; 6,664,264; 6,664,265; 6,667,312; 6,670,372; 6,677,347; 6,677,348; 6,677,349; 6,683,088; European Patent 0 394 026; U.S. Pat. Publication Nos. 2002/0016332; 2002/0055517; 2002/0110840; 2003/0133913; 2003/0199538; and 2004/0014779; and International Patent Publication Nos. WO 01/74343; WO 02/46749 WO 02/102377; WO 03/020889; WO 03/043572; WO 03/045391; and WO 03/103584.
Additional examples of small molecule IRMs include certain purine derivatives (such as those described in U.S. Pat. Nos. 6,376,501, and 6,028,076), certain imidazoquinoline amide derivatives (such as those described in U.S. Pat. No. 6,069,149), certain imidazopyridine derivatives (such as those described in U.S. Pat. No. 6,518,265), certain benzimidazole derivatives (such as those described in U.S. Pat. No. 6,387,938), certain derivatives of a 4-aminopyrimidine fused to a five membered nitrogen containing heterocyclic ring (such as adenine derivatives described in U.S. Pat. Nos. 6,376,501; 6,028,076 and 6,329,381; and in WO 02/085905), and certain 3-β-D-ribofuranosylthiazolo[4,5-d]pyrimidine derivatives (such as those described in U.S. Publication No. 2003/0199461).
Other IRMs include large biological molecules such as oligonucleotide sequences. Some IRM oligonucleotide sequences contain cytosine-guanine dinucleotides (CpG) and are described, for example, in U.S. Pat. Nos. 6,194,388; 6,207,646; 6,239,116; 6,339,068; and 6,406,705. Some CpG-containing oligonucleotides can include synthetic immunomodulatory structural motifs such as those described, for example, in U.S. Pat. Nos. 6,426,334 and 6,476,000. Other IRM nucleotide sequences lack CpG sequences and are described, for example, in International Patent Publication No. WO 00/75304.
Other IRMs include biological molecules such as aminoalkyl glucosaminide phosphates (AGPs) and are described, for example, in U.S. Pat. Nos. 6,113,918; 6,303,347; 6,525,028; and 6,649,172.
One IRM compound has been shown to effective for removing freshly applied tattoos (Solis et al., Dermatol Surg. 28:83–87 (2002)). Solis et al. tattooed a group of guinea pigs with a commonly used set of tattoo inks. Topical treatment of the tattooed area with 5% imiquimod (1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine) cream, marketed as ALDARA (3M Pharmaceuticals, St. Paul, Minn.), was initiated within six hours of the tattoo application and continued for seven days. At the conclusion of the treatment period, no pigment of any color was visible in the tattooed regions. Thus, an IRM compound applied to a recently tattooed area has been shown to remove tattoo ink pigments while they are still in the free extracellular (i.e., interstitial) space of the dermis. However, a need remains for methods of removing mature tattoos—i.e., tattoo images that are days, not merely hours, old.